Immune mediated acute glomerulonephritis (GN) remains an important cause of renal injury leading to chronic renal failure and end stage renal disease. Studies of human and experimental models of GN have led to a better understanding of the inflammatory mediators, both humoral and cellular, involved in the production of immunologic glomerular injury. The response of intrinsic glomerular cells to such mediators, however, is still largely unexplored. One cell type which is frequently involved in GN is the glomerular visceral epithelial cell (GEC). The response of GEC to injury is limited, consisting mainly of alterations in morphology and proliferation. The possibility also exists that GEC play a functional role in modulating glomerular injury through the production or inactivation of inflammatory mediators. The major goal of the studies outlined here is to achieve a better understanding of the response of GEC to inflammatory mediators by studying the interaction of GEC grown in cell culture with several mediators which participate in models of GN involving GEC injury. Specifically, we will: 1) Study the interactions of antibodies, immune complexes and the complement system ( both early and late portions) as well a mediators derived from inflammatory cells (neutrophils and macrophages) and platelets with GEC in culture. The ability of these substances to produce GEC injury, stimulate or inhibit release of prostaglandins, oxygen radicals and proteases by GEC and alter GEC protein synthesis will be evaluated: 2) Study the proliferative response of GEC in culture to inflammatory mediators. This will include substances produced during the course of initiation of immune mediated injury (e.g. immune complexes, complement activation products) and substances released from inflammatory cells and platelets (e.g. oxygen radicals, prostaglandins, lymphokines, growth factors, cationic proteins); 3) Explore mechanisms of inhibition of GEC proliferation by heparin. The inhibitory effect of anticoagulant heparin plus serum on these cells will be further characterized. The studies described here will lead to a better understanding of the response of GEC to immune mediated glomerular injury and their role in modulating such injury. Eventually this should lead to the ability to design therapies to block any deleterious responses and help preserve renal function.